Mouse artificial chromosome vector and use thereof

Abstract

A mouse artificial chromosome vector is stable in rodent cells, tissues, and/or individuals, specifically a mouse artificial chromosome vector derived from a mouse chromosome selected from mouse chromosome 10 and mouse chromosome 16. A cell or a non-human animal may include the vector. The vector may be used for producing proteins and human antibodies.

1 . A non-human animal, comprising a mouse vector, the vector comprising:
 a natural centromere derived from a mouse chromosome 10;   a mouse-chromosome-derived long-arm fragment formed by deleting gene Gm8155 and the entire long-arm region of mouse chromosome 10 distal to gene Gm8155 to substantially remove endogenous genes in the mouse chromosome; and   a telomere sequence,   wherein the vector is stably retained in cells and tissues of a mouse or rat at a retention rate of at least 90%, and   wherein the mouse artificial chromosome vector is capable of transmission to a progeny of the mouse or rat.   
     
     
         2 . The animal of  claim 1 , wherein the vector comprises a mouse artificial chromosome vector contained in the deposited cell line DT40 (10MAC) T5-26 (NITE BP-02656). 
     
     
         3 . The animal of  claim 1 , which is a rodent. 
     
     
         4 . The animal of  claim 3 , wherein the rodent is a mouse or a rat. 
     
     
         5 . The animal of  claim 1 , which is capable of producing human antibodies. 
     
     
         6 . The animal of  claim 1 , wherein the vector further comprises at least one DNA sequence insertion site. 
     
     
         7 . The animal of  claim 1 , wherein the vector further comprises a reporter gene, a selection marker gene, or a combination thereof. 
     
     
         8 . The animal of  claim 1 , wherein the vector further comprises an exogenous DNA sequence. 
     
     
         9 . The animal of  claim 8 , wherein the exogenous DNA sequence is a human DNA sequence. 
     
     
         10 . The animal of  claim 8 , wherein the exogenous DNA sequence is a DNA sequence of a human-chromosome-derived long arm or short arm. 
     
     
         11 . The animal of  claim 8 , wherein the exogenous DNA sequence is a human immunoglobulin heavy chain gene, a human immunoglobulin light chain gene, or a combination thereof. 
     
     
         12 . The animal of  claim 8 , wherein the exogenous DNA sequence is a gene or DNA sequence encoding a polypeptide selected from the group consisting of a cytokine, hormone, growth factor, nutritional factor, hematopoietic factor, coagulation factor, hemolysis factor, G protein-coupled receptor, enzyme, or a gene or DNA sequence used for treatment of a disease elected from the group consisting of a tumor, muscular dystrophy, hemophilia, neurodegenerative disease, autoimmune disease, allergic disease, genetic disease or a gene or DNA sequence encoding a T-cell receptor or a human leukocyte antigen. 
     
     
         13 . The animal of  claim 1 , comprising
 a disrupted endogenous gene corresponding to an exogenous DNA contained in the mouse artificial chromosome vector, or   having lowered expression of the endogenous gene relative to an otherwise identical animal without the vector.   
     
     
         14 . A method for producing a human antibody or antibodies, the method comprising:
 allowing the animal of  claim 1 , which comprises the mouse artificial chromosome vector comprising human antibody heavy chain and light chain genes or gene loci to produce the human antibody or antibodies, and capable of producing human antibodies; and   collecting the human antibody or antibodies.   
     
     
         15 . The method of  claim 14 , wherein the vector comprises a mouse artificial chromosome vector contained in the deposited cell line DT40 (10MAC) T5-26 (NITE BP-02656). 
     
     
         16 . The method of  claim 14 , wherein the human antibody light chain gene or gene locus is the human antibody λ light chain gene or gene locus and/or the human antibody κ light chain gene or gene locus.